(1) Field of the Invention
This Invention relates to improvements in volume-selected NMR spectroscopy.
(2) Prior Art
With the recent development of wholebody NMR spectroscopy, there is a need to find a technique to obtain high quality spectra from a particular volume in space. In this way, biochemical data may be obtained from one organ, or preferably from selected regions within such an organ, in a non-invasive manner. There have been a number of methods proposed to do this and these fall into three broad groups. They are:
(1) The use of a pulse train which exploits the pulse inhomogeneity to select a volume within a sample by selecting only the region with a particular pulse angle;
(2) The use of some form of field profile technique to produce a region of high magnetic field homogeneity within a larger region where the field changes sharply with position. (The result is that high resolution spectra are obtained from the region of interest whilst signals arising from the inhomogeneous region are so broad that they may be eliminated from spectra.)
In principle, methods (1) and (2) generally rely upon physical movement of the sample within the system to obtain signals from various regions.
(3) The third method is to use a combination of frequency selective radio-frequency pulses in the presence of magnetic field gradients to effect volume selection. It appears that this third approach may well be the most useful as it combines the versatility of complete software control of gradients and selective excitation pulses to produce volume-selection in all three directions. As well, the technique may be image encoded, the consequence being that the position of the selected volume is accurately known.
For effective use in practice, strong signal-to-noise must be obtained from any particular technique. To do this, we must keep three objects in mind:
(1) Maximum signal should be excited within the confines of the slice of choice:
(2) Magnetization of interest should remain in the transverse plane for as little time as possible particularly while applied field gradients are present. The resultant loss of coherence leads to a reduction in signal strength: and
(3) The spectra should be obtained after applied gradients have reached zero amplitude so that line widths are narrow and the chemical shifts displayed are those present independent of volume selection.
These last two points combined mean it is preferable to have the magnetization aligned with the field axis while gradients are being changed.
Some of the methods proposed previously for volume-selection include, DRESS, [Depth-resolved surface-coil in spectroscopy (DRESS) in vivo .sup.1 H, .sup.31 P, and .sup.31 C NMR, P. A. Bottomley, T. H. Foster and R. D. Darrow, J. Magn. Reson. 59, 338, (1984)]; VSE (H. Post, D. Ratzel and P. Brunner, West German Patent No. 3209263-6, Mar. 13, 1982, and also Volume-selected Excitation. A novel approach to topical NMR. W. P. Aue, S. Miller, T. A. Cross and J. Seeliq. J. Magn. Reson. 56, 350 (1984)]: and ISIS, [Image-selected in
vivo Spectroscopy (ISIS). A new technique for spatially selective NMR Spectrosscopy. R. J. Ordidge, A. Connelly and J. A. B. Lohman. J. Magn. Reson. 66, 283, (1986)]; These methods involve the application of narrow bandwidth radio-frequency excitation in the presence of a field gradient applied across the sample. The gradient is then switched off and the signal acquired. In principle, these methods can be extended to include slicing in all directions.
The known methods can be summarised as follows:
(1) DRESS uses a selective rf pulse in the presence of an applied field gradient to excite a slice of magnetization. Gradient reversal is then used to form a spin-echo which refocusses the off-resonance effects of the pulse. The major drawback of this method is that the magnetization of interest lies in the transverse plane during refocussing and so is T.sub.2 contrasted. Furthermore the acquired signals are either gradient broadened or reduced in intensity or both because of the need to allow gradient fall to occur before switching the receiver on. Volume selection is only one dimensional and the finite dimensions of the receiver coil are used to limit the volume in the plane of the slice.
(2) ISIS is based on a phase inversion between signals in the slice of interest and those arising from outside. This is carried out by applying an inversion pulse tailored to the appropriate bandwidth in the presence of a gradient. The volume-selected spectrum is obtained by adding and subtracting appropriate combinations of phase inverted signals in the computer memory. The primary disadvantage of ISIS is that it relies on the ability of the computer to distinguish between the small signals within the volume of interest and the residual signal which will often be several orders of magnitude stronger. This, of course, is reliant upon the dynamic range of the computer memory as well as the spectrometer preamplifier and receiver systems.
(3) SPARS uses a refocussing pulse to form a spin-echo in the presence of an applied field gradient. A selective pulse of appropriate bandwidth is then applied to rotate the magnetization in the slice of interest back to the applied field direction following which the gradient is collapsed. This is carried out in all directions to yield the desired volume of interest which can then be read out with a single pulse. In this method the magnetization of interest suffers the effect of three gradient rises or falls while it is in the transverse plane for each direction of slicing which means any irrecoverable losses associated with gradient rises or falls are extreme. The time for refocussing is extended because gradient changes require finite time whereupon T.sub.2 relaxation becomes important. The sensitivity of this technique is also dependent on efficient refocussing and on applying the selective pulse at precisely the correct moment. It appears that the phase evolution of the signal during this pulse also contributes to the weakening of signal strength.
(4) VSE uses a composite pulse cluster in the presence of a field gradient for slice selection. It is of the form .pi./4(x).pi./2[x].pi./4(x) where, by convention, .pi./4(x) signifies a 45.degree. selective pulse of some sort applied along the x axis and .pi./2[x] signifies a 90.degree. pulse applied to all spins. Ideally the spins within the slice feel the sum of all pulses, i.e. a .pi. rotation while those outside feel only a 90.degree. rotation and their transverse phase coherence is dephased by the slice gradient. However, off-resonance effects of the hard pulse mean that signals arising from outside of the slice are not eliminated in one pass through the pulse cluster. In fact even by using a phase cycle to implement an add/substract routine, there is a significant residual signal. The VSE technique is discussed in [Discrete isolation from Gradient-Governed Elimination of Resonances. DIGGER, a new technique for in vivo volume-selected spectroscopy. D. M. Doddrell, J. M. Bulsing, G. J. Galloway, W. M. Brooks, J. Field, M. G. Irving and H. Baddeley. J. Magn. Reson. 70, 319 (1986)], showing how this residual signal reduces the quality of the final spectrum.